Protein kinases specific for tyrosine have been associated with the control of cell growth. A rabbit antiserum and a mouse monoclonal antibody both specific for phosphotyrosine were developed to identify and purify phosphotyrosine-containing proteins. Using these antibodies, we are presently studying phosphorylation of cellular proteins in response to epidermal growth factor (EGF). A panel of drugs known to effect cell proliferation and other growth factor-induced responses were tested for their effects on EGF-induced phosphorylation. Several classes of drugs have been identified which inhibit both cell proliferation and EGF-induced phosphorylation. We are currently examining the mechanisms by which these drugs act, looking particularly closely at the effects of the drugs on the phosphorylation of the EGF receptor. We believe that these drugs act through mechanisms active in the regulation of normal cell growth. The activity of growth-factor receptors may be modulated by metabolic and physiological state of the cell and, thereby, modulate cell proliferation. We will extend these studies to include other growth factors and biologically active substances. Also, we will compare the regulation of growth-factor receptors in normal and senescent cells. (N)